
Fundación Jiménez Díaz University Hospital, Pathology Department,
Madrid, Spain,
3
Fundación Jiménez Díaz University Hospital, Health
Research Institute IIS‐FJD, Madrid, Spain, Department of Hematology,
Madrid, Spain,
4
Fundación Jiménez Díaz University Hospital, Health
Research Institute IIS‐FJD, CIBERONC, Madrid, Spain., Department of
Hematology, Madrid, Spain,
5
Instituto de Investigación Sanitaria Puerta
de Hierro‐Segovia de Arana, CIBERONC, Madrid, Spain, Lymphoma
Research Group, Medical Oncology Department, Madrid, Spain,
6
Instituto
de Investigación Sanitaria Puerta de Hierro‐Segovia de Arana, Madrid,
Spain, Lymphoma Research Group, Medical Oncology Department,
Madrid, Spain,
7
Hospital Universitario 12 de Octubre, Madrid, Spain,
Pathology Department, Madrid, Spain,
8
Hospital MD Anderson Cancer
Center, CIBERONC, Madrid, Spain, Pathology Department, Madrid, Spain,
9
Hospital Virgen de la Salud, CIBERONC, Toledo, Spain, Pathology
Department, Toledo, Spain,
10
Hospital Universitario Ramón y Cajal,
CIBERONC, Madrid, Spain, Pathology Department, Madrid, Spain,
11
Hospital Universitario Puerta de Hierro‐Segovia de Arana, CIBERONC,
Madrid, Spain, Pathology Department, Madrid, Spain,
12
Hospital Uni-
versitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain,
Pathology Department, Barcelona, Spain,
13
Hospitalario Universitario de
Salamanca (HUS/IBSAL), Salamanca, Spain, Haematology Department,
Salamanca, Spain,
14
Hospital Universitario Virgen del Rocío, CIBERONC,
Sevilla, Spain, Laboratory, Sevilla, Spain,
15
Kura Oncology Inc., Kura
Oncology Inc., San Diego, California, USA
Introduction: Peripheral T‐cell Lymphomas (PTCLs) are aggressive
tumours with unfavourable prognosis, with around 30% overall sur-
vival (OS) after 5 years. Histological and molecular studies have
revealed a striking degree of heterogeneity, with three major PTCL
subtypes defined. Consistent diagnosis and prognostication are still
difficult to achieve, because of the difficulty of reproducing results,
and the dearth of clinically applicable prognostic biological markers.
Methods: We have analyzed a series of 105 PTCL cases (66 angioim-
munoblastic T‐cell lymphoma, AITL; 21 PTCL‐not otherwise specified,
PTCL‐NOS; and 18 PTCL‐with T follicular helper phenotype, PTCL‐
TFH) patients using a customized NanoString platform that includes
208 genes associated with T‐cell differentiation, oncogenes and tumor
suppressor genes, deregulated pathways and stromal cell sub-
populations. Specifically, the platform includes genes expressed by the
multiple cell types present in PTCL specimens, together with normal T‐
cell populations. These are used to try and enable the deconvolution of
the T‐cell lymphoma microenvironment, and thereby develop an in-
tegrated perspective on the cell composition of PTCL tumor
specimens.
Results: A comparative analysis of the various histological types of
PTCL (AITL, PTCL‐NOS and PTCL‐TFH) showed specific sets of genes
to be associated with each of the diagnoses, including TFH markers,
cytotoxic markers and genes whose expression was a surrogate for
specific cellular subpopulations, including follicular dendritic cells,
mast cells and genes belonging to specific cell‐survival pathways (NF‐
κB). Unsupervised analysis of the expression of the genes here
studied revealed clusters of co‐regulated genes that identified the
main cell components of the tumor. The analysis did not reveal any
differences in survival probability associated with the histological
sub‐classification, but did identify specific genes and gene sets whose
expression was associated with changes in survival probability for
each of the PTCL subtypes, independently of the clinical variables
included in the International Prognostic Index (IPI). These included a
B‐cell gene set in cases of AITL, the expression of proliferation
markers in PTCL‐NOS, and the expression of cytotoxic markers in
cases with a diagnosis of PTCL‐TFH. For each PTCL lymphoma type, a
multivariate analysis identified genes that allow the series of cases to
be stratified into different risk groups. This was validated for AITL in
an independent series of 54 additional cases.
Conclusions: In summary, our study supports the current division of
PTCL into these three categories (AITL, PTCL‐NOS and PTCL‐TFH),
identifies gene sets potentially useful for this classification and rec-
ognizes the expression of B‐cell genes as an IPI‐independent prog-
nostic factor for AITL subtype.
EA – previously submitted to regional or national meetings (up to
1000 attendees).
The research was funded by: The research was supported by grants
from Instituto de Salud Carlos III, from Ministerio de Economía,
Industria y Competitividad, Asociación Española Contra el Cáncer
(AECC), Comunidad Autónoma de Madrid and Centre for Biomedical
Network Research on Cancer (CIBERONC): SAF2013‐47416‐R,
CIBERONC‐ISCIII (CB16/12/00291), ISCIII‐MINECO‐AES‐FEDER
(Plan Estatal I + D + I 2013‐2016), ISCIII‐MINECO AES‐FEDER
(Plan Estatal I + D + I 2017‐2020), AECC PROYE18054PIRI, CAM
B2017/BMD‐3778, PIC97/2017_FJD, PIE15/0081, PI17/00272,
PIE16/01294, GILEAD (GL18/00019) and PIC 041‐19. L. Tomas‐
Roca was funded by Marie Skłodowska‐Curie Individual Fellowship
(No 882597).
Keywords: Genomics, Epigenomics, and Other ‐Omics, Diagnostic and
Prognostic Biomarkers, Aggressive T‐cell non‐Hodgkin lymphoma
Conflicts of interests pertinent to the abstract
M. Án. Piris
Consultant or advisory role: Millenium/Takeda, Celgene, Gilead,
Jansen, NanoString, Kyowa Kirin
Research funding: Millenium/Takeda, Gilead, Kura
229 | MUTATIONAL ANALYSIS OF THE DIFFERENT NODAL
PERIPHERAL T‐CELL LYMPHOMA SUBCLASSES
L. Tomas‐Roca
1
, M. Rodriguez
2
, R. Alonso‐Alonso
2
, L. Cereceda
2
, S.
M. Rodriguez‐Pinilla
2
, J. Borregón
1
, R. Manso
1
, T. Villaescusa
3
, R.
Córdoba
4
, M. Sánchez‐Beato
5
, I. Fernández‐Miranda
6
, C. Barcena
7
, J.
F García
8
, M. Mollejo
9
, M. García‐Cosio
10
, P. Martin‐Acosta
11
, F.
Climent
12
, D. Caballero
13
, M. A. Piris
14
1
Instituto de Investigación Sanitaria Fundación Jiménez Díaz, Pathology
Department, Madrid, Spain,
2
Instituto de Investigación Sanitaria
Fundación Jiménez Díaz, Centro de Investigación Biomédica en Red de
Cáncer (CIBERONC), Pathology Department, Madrid, Spain,
3
Hospital
SUPPLEMENT ABSTRACTS
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